DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study

Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism.     

In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum leprieurii Guill. et Perr

Chemical investigation of the roots and fruits of Zanthoxylum leprieurii Guill. et Perr. led to the isolation of three new alkaloids including two acridone derivatives, 3-hydroxy-1,4-dimethoxy-10-methyl-9-acridone (2) and 3-hydroxy-1,2-dimethoxy-10-methyl-9-acridone (3) named helebelicine A and B, respectively, and one secobenzo[c]phenantridine, 10-O-demethyl-12-O-methylarnottianamide (10), together with thirteen other compounds. The structures of compounds 2, 3 and 10 as well as those of the known compounds were elucidated by using spectroscopic methods and by comparison with reported data. The brine-shrimp (artemia salina) lethality bioassay of the chloroform extract of the fruits showed modest cytotoxicity with LD₅₀ at 13.1 μg/mL. Isolated compounds 1, 4–6 were found to be moderately active against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1) with IC₅₀ values ranging from 27 to 77 μM. In contrast to the positive control etoposide used, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells WS1 with IC₅₀ of 51 ± 8 μM and 4.3 ± 0.4 μM, respectively.     

In Vivo Screening of Hepatocellular Carcinoma Using AC Susceptibility of Anti-Alpha Fetoprotein-Activated Magnetic Nanoparticles

With antibody-mediated magnetic nanoparticles (MNPs) applied in cancer examinations, patients must pay at least twice for MNP reagents in immunomagnetic reduction (IMR) of in vitro screening and magnetic resonance imaging (MRI) of in vivo tests. This is because the high maintenance costs and complex analysis of MRI have limited the possibility of in vivo screening. Therefore, this study proposes novel methods for in vivo screening of tumors by examining the AC susceptibility of bound MNPs using scanning superconducting-quantum-interference-device (SQUID) biosusceptometry (SSB), thereby demonstrating high portability and improved economy. The favorable agreement between in vivo tests using SSB and MRI demonstrated the feasibility of in vivo screening using SSB for hepatocellular carcinoma (HCC) targeted by anti-alpha fetoprotein (AFP)-mediated MNPs. The magnetic labeling was also proved by in vitro tests using SSB and biopsy assays. Therefore, patients receiving bioprobe-mediated MNPs only once can undergo in vivo screening using SSB in the future.     

Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre

Background

Empyema is an increasingly frequent clinical problem worldwide, and has substantial morbidity and mortality. Our objectives were to identify the clinical, surgical and microbiological features, and management outcomes, of empyema.

Methods

A retrospective observational study over 12 years (1999–2010) was carried out at The Heart Hospital, London, United Kingdom. Patients with empyema were identified by screening the hospital electronic ‘Clinical Data Repository’. Demographics, clinical and microbiological characteristics, underlying risk factors, peri-operative blood tests, treatment and outcomes were identified. Univariable and multivariable statistical analyses were performed.

Results

Patients (n = 406) were predominantly male (74.1%); median age = 53 years (IQR = 37–69). Most empyema were community-acquired (87.4%) and right-sided (57.4%). Microbiological diagnosis was obtained in 229 (56.4%) patients, and included streptococci (16.3%), staphylococci (15.5%), Gram-negative organisms (8.9%), anaerobes (5.7%), pseudomonads (4.4%) and mycobacteria (9.1%); 8.4% were polymicrobial. Most (68%) cases were managed by open thoracotomy and decortication. Video-assisted thoracoscopic surgery (VATS) reduced hospitalisation from 10 to seven days (P = 0.0005). All-cause complication rate was 25.1%, and 28 day mortality 5.7%. Predictors of early mortality included: older age (P = 0.006), major co-morbidity (P = 0.01), malnutrition (P = 0.001), elevated red cell distribution width (RDW, P<0.001) and serum alkaline phosphatase (P = 0.004), and reduced serum albumin (P = 0.01) and haemoglobin (P = 0.04).

Conclusions

Empyema remains an important cause of morbidity and hospital admissions. Microbiological diagnosis was only achieved in just over 50% of cases, and tuberculosis is a notable causative organism. Treatment of empyema with VATS may reduce duration of hospital stay. Raised RDW appears to associate with early mortality.     

Sieve element occlusion provides resistance against Aphis gossypii in TGR-1551 melons

Feeding behavior and plant response to feeding were studied for the aphid Aphis gossypii Glover on susceptible and resistant melons(cv.Iroquois and TGR-1551,respectively).Average phloem phase bout duration on TGR-1551 was<7% of the duration on Iroquois.Sixty-seven percent of aphids on TGR-1551 never produced a phloem phase that attained ingestion(EPG waveform E2)in contrast to only 7% of aphids on Iroquois.Average bout duration of waveform E2(scored as zero if phloem phase did not attain E2)on TGR-1551 was<3% of the duration on Iroquois.Conversely,average bout duration of EPG waveform El(sieve element salivation)was 2.8 times greater on TGR-1551 than on Iroquois.In a second experiment,liquid nitrogen was used to rapidly cryofix leaves and aphids within a few minutes after the aphids penetrated a sieve element.Phloem near the penetration site was then examined by confocal laser scanning microscopy.Ninety-six percent of penetrated sieve elements were occluded by protein in TGR-1551 in contrast to only 28% in Iroquois.Usually in TGR-1551,occlusion was also observed in nearby nonpenetrated sieve elements.Next,a calcium channel blocker,trivalent lanthanum,was used to prevent phloem occlusion in TGR-1551,and A.gossypii feeding behavior and the plants phloem response were compared between lanthanum-treated and control TGR-1551.Lanthanum treatment eliminated the sieve element protein occlusion response and the aphids readily ingested phloem sap from treated plants.This study provides strong evidence that phloem occlusion is a mechanism for resistance against A.gossypii in TGR-1551.     

Rapid Immune Colloidal Gold Strip for Cetacean Meat Restraining Illegal Trade and Consumption: Implications for Conservation and Public Health

The consumption of cetacean meat is geographically common and often of undetermined sustainability. Besides, it can expose humans to contaminants and zoonotic pathogens. The illegality of possessing cetacean meat was likely under-reported in some countries due to lack of attention paid by the officials although DNA analysis of market products helped to show such practices. We developed two monoclonal antibodies against synthetic peptides of myoglobin (Mb) for constructing a rapid immune colloidal gold strip. Only cetacean Mb is capable of binding to both antibodies and presents positive signal while the Mb from other animals can bind only 1 of the antibodies and presents negative result. The strip for cetacean meat would be an applicable and cost-effective test for field inspectors and even the general public. It contributes to increase the reporting capacity and coverage of illegal cetacean meat possession, which has implications for global cetacean conservation and public health.     

Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?

JBIC Journal of Biological Inorganic Chemistry - Platinum anticancer therapeutics are widely used in a variety of chemotherapy regimens. Recent work has revealed that the cytotoxicity of...